title: Evidence for novel hepaciviruses in rodents.
abstract: Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Jan Felix
authors.initials: JF
authors.lastname: Drexler
authors.forename: Victor Max
authors.initials: VM
authors.lastname: Corman
authors.forename: Marcel Alexander
authors.initials: MA
authors.lastname: Müller
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Lukashev
authors.forename: Anatoly
authors.initials: A
authors.lastname: Gmyl
authors.forename: Bruno
authors.initials: B
authors.lastname: Coutard
authors.forename: Alexander
authors.initials: A
authors.lastname: Adam
authors.forename: Daniel
authors.initials: D
authors.lastname: Ritz
authors.forename: Lonneke M
authors.initials: LM
authors.lastname: Leijten
authors.forename: Debby
authors.initials: D
authors.lastname: van Riel
authors.forename: Rene
authors.initials: R
authors.lastname: Kallies
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Klose
authors.forename: Florian
authors.initials: F
authors.lastname: Gloza-Rausch
authors.forename: Tabea
authors.initials: T
authors.lastname: Binger
authors.forename: Augustina
authors.initials: A
authors.lastname: Annan
authors.forename: Yaw
authors.initials: Y
authors.lastname: Adu-Sarkodie
authors.forename: Samuel
authors.initials: S
authors.lastname: Oppong
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bourgarel
authors.forename: Daniel
authors.initials: D
authors.lastname: Rupp
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoffmann
authors.forename: Mathias
authors.initials: M
authors.lastname: Schlegel
authors.forename: Beate M
authors.initials: BM
authors.lastname: Kümmerer
authors.forename: Detlev H
authors.initials: DH
authors.lastname: Krüger
authors.forename: Jonas
authors.initials: J
authors.lastname: Schmidt-Chanasit
authors.forename: Alvaro Aguilar
authors.initials: AA
authors.lastname: Setién
authors.forename: Veronika M
authors.initials: VM
authors.lastname: Cottontail
authors.forename: Thiravat
authors.initials: T
authors.lastname: Hemachudha
authors.forename: Supaporn
authors.initials: S
authors.lastname: Wacharapluesadee
authors.forename: Klaus
authors.initials: K
authors.lastname: Osterrieder
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
authors.forename: Sonja
authors.initials: S
authors.lastname: Matthee
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.forename: Chantal
authors.initials: C
authors.lastname: Reusken
authors.forename: Eric M
authors.initials: EM
authors.lastname: Leroy
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
mesh_terms: D000818:Animals; D001483:Base Sequence; D002415:Cats; D004285:Dogs; D019143:Evolution, Molecular; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D006526:Hepatitis C / Q000097:blood / Q000235:genetics / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood*; D006520:Hepatitis, Animal / Q000097:blood / Q000235:genetics / Q000821:virology; D006736:Horses; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012377:Rodentia / Q000097:blood / Q000821:virology
chemical_list: D018937:Hepatitis C Antibodies; D012367:RNA, Viral